A decreased physical fitness and impaired social functioning has been reported in patients and survivors of childhood cancer. This is influenced by the negative effects of disease and treatment of ...childhood cancer and by behavioural and social elements. Exercise training for adults during or after cancer therapy has frequently been reported to improve physical fitness and social functioning. More recently, literature on this subject became available for children and young adults with cancer, both during and after treatment.
This review aimed to evaluate the effect of a physical exercise training intervention (at home, at a physical therapy centre, or hospital based) on the physical fitness of children with cancer, in comparison with the physical fitness in a care as usual control group. The intervention needed to be offered within the first five years from diagnosis.The second aim was to assess the effects of a physical exercise training intervention in this population on fatigue, anxiety, depression, self efficacy, and health-related quality of life and to assess the adverse effects of the intervention.
For this review the electronic databases of CENTRAL, MEDLINE, EMBASE, CINAHL, PEDro, and ongoing trial registries were searched on 6 September 2011. In addition, a handsearch of reference lists and conference proceedings was performed in that same month.
The review included randomised controlled trials (RCTs) and clinical controlled trials (CCTs) that compared the effects of physical exercise training with no training, in people who were within the first five years of their diagnosis of childhood cancer.
By the use of standardised forms two review authors independently identified studies meeting the inclusion criteria, performed the data extraction, and assessed the risk of bias. Quality of the studies was rated by using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) criteria.
Five articles were included in this review: four RCTs (14, 14, 28, and 51 participants) and one CCT (24 participants). In total 131 participants (74 boys, 54 girls, three unknown) were included in the analysis, all being treated for childhood acute lymphoblastic leukaemia (ALL). The study interventions were all implemented during chemotherapy treatment.The duration of the training sessions ranged from 15 to 60 minutes per session. Both the type of intervention, as well as the intervention period, which ranged from 10 weeks to two years, varied in all the included studies. In all included studies the control group received care as usual.All studies had methodological limitations, such as small numbers of participants, unclear randomisation methods, and single-blind study designs in case of an RCT.Cardiorespiratory fitness was studied by the use of the nine-minute run-walk test, the timed up-and-down stairs test, and the 20-m shuttle run test. Only the up-and-down stairs test showed significant differences between the intervention and the control group, in favour of the intervention group (P value = 0.05, no further information available).Bone mineral density was assessed in one study, in which a statistically significant difference in favour of the exercise group was identified (standardised mean difference (SMD) 1.07; 95% confidence interval (CI) 0.48 to 1.66; P value < 0.001). Body mass index was assessed in two studies. The pooled data on this item did not show a statistically significant difference between the intervention and control study group.Flexibility was assessed in three studies. In one study the active ankle dorsiflexion method was used to assess flexibility and the second study they used the passive ankle dorsiflexion test. No statistically significant difference between the intervention and control group was identified with the active ankle dorsiflexion test, whereas with the passive test method a statistically significant difference in favour of the exercise group was found (SMD 0.69; 95% CI 0.12 to 1.25; P value = 0.02). The third study assessed body flexibility by the use of the sit-and-reach distance test; no statistically significant difference between the intervention and control group was identified.One study assessed the effects of an inspiratory muscle training programme aimed to train the lung muscles and increase physical fitness. This study reported no significant effect on either inspiratory or expiratory muscle strength. Two other studies using either knee and ankle strength changes by hand-held dynamometry or the number of completed push-ups (with knees on the ground) and a peripheral quantitative computed tomography of the tibia to determine the muscle mass did not identify statistically significant differences in muscle strength/endurance.The level of daily activity, health-related quality of life, fatigue, and adverse events were assessed in one study only; for all these items no statistically significant differences between the intervention and control group were found.None of the included studies evaluated the outcomes activity energy expenditure, time spent exercising, anxiety and depression, or self efficacy.
The effects of physical exercise training interventions for childhood cancer participants are not yet convincing due to small numbers of participants and insufficient study methodology. Despite that, first results show a trend towards an improved physical fitness in the intervention group compared to the control group. Changes in physical fitness were seen by improved body composition, flexibility, and cardiorespiratory fitness. However, the evidence is limited and these positive effects were not found for the other assessed outcomes, such as muscle strength/endurance, the level of daily activity, health-related quality of life, and fatigue. There is a need for more studies with comparable aims and interventions, using higher numbers of participants and for studies with another childhood cancer population than ALL only.
Background
Improvements in diagnostics and treatment for paediatric malignancies resulted in a major increase in survival. However, childhood cancer survivors (CCS) are at risk of developing adverse ...effects caused by multimodal treatment for their malignancy. Nephrotoxicity is a known side effect of several treatments, including cisplatin, carboplatin, ifosfamide, radiotherapy and nephrectomy, and can cause glomerular filtration rate (GFR) impairment, proteinuria, tubulopathy, and hypertension. Evidence about the long‐term effects of these treatments on renal function remains inconclusive. It is important to know the risk of, and risk factors for, early and late adverse renal effects, so that ultimately treatment and screening protocols can be adjusted. This review is an update of a previously published Cochrane Review.
Objectives
To evaluate existing evidence on the effects of potentially nephrotoxic treatment modalities on the prevalence of renal dysfunction in survivors treated for childhood cancer with a median or mean survival of at least one year after cessation of treatment, where possible in comparison with the general population or CCS treated without potentially nephrotoxic treatment. In addition, to evaluate evidence on associated risk factors, such as follow‐up duration, age at time of diagnosis and treatment combinations, as well as the effect of doses.
Search methods
On 31 March 2017 we searched the following electronic databases: CENTRAL, MEDLINE and Embase. In addition, we screened reference lists of relevant studies and we searched the congress proceedings of the International Society of Pediatric Oncology (SIOP) and The American Society of Pediatric Hematology/Oncology (ASPHO) from 2010 to 2016/2017.
Selection criteria
Except for case reports, case series and studies including fewer than 20 participants, we included studies with all study designs that reported on renal function (one year or longer after cessation of treatment), in CCS treated before the age of 21 years with cisplatin, carboplatin, ifosfamide, radiation involving the kidney region, a nephrectomy, or a combination of two or more of these treatments. When not all treatment modalities were described or the study group of interest was unclear, a study was not eligible for the evaluation of prevalence. We still included it for the assessment of risk factors if it had performed a multivariable analysis.
Data collection and analysis
Two review authors independently performed study selection, 'Risk of bias' assessment and data extraction using standardised data collection forms. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions.
Main results
Apart from the remaining 37 studies included from the original review, the search resulted in the inclusion of 24 new studies. In total, we included 61 studies; 46 for prevalence, six for both prevalence and risk factors, and nine not meeting the inclusion criteria, but assessing risk factors. The 52 studies evaluating the prevalence of renal dysfunction included 13,327 participants of interest, of whom at least 4499 underwent renal function testing. The prevalence of adverse renal effects ranged from 0% to 84%. This variation may be due to diversity of included malignancies, received treatments, reported outcome measures, follow‐up duration and the methodological quality of available evidence.
Seven out of 52 studies, including 244 participants, reported the prevalence of chronic kidney disease, which ranged from 2.4% to 32%.
Of these 52 studies, 36 studied a decreased (estimated) GFR, including at least 432 CCS, and found it was present in 0% to 73.7% of participants. One eligible study reported an increased risk of glomerular dysfunction after concomitant treatment with aminoglycosides and vancomycin in CCS receiving total body irradiation (TBI). Four non‐eligible studies assessing a total cohort of CCS, found nephrectomy and (high‐dose (HD)) ifosfamide as risk factors for decreased GFR. The majority also reported cisplatin as a risk factor. In addition, two non‐eligible studies showed an association of a longer follow‐up period with glomerular dysfunction.
Twenty‐two out of 52 studies, including 851 participants, studied proteinuria, which was present in 3.5% to 84% of participants. Risk factors, analysed by three non‐eligible studies, included HD cisplatin, (HD) ifosfamide, TBI, and a combination of nephrectomy and abdominal radiotherapy. However, studies were contradictory and incomparable.
Eleven out of 52 studies assessed hypophosphataemia or tubular phosphate reabsorption (TPR), or both. Prevalence ranged between 0% and 36.8% for hypophosphataemia in 287 participants, and from 0% to 62.5% for impaired TPR in 246 participants. One non‐eligible study investigated risk factors for hypophosphataemia, but could not find any association.
Four out of 52 studies, including 128 CCS, assessed the prevalence of hypomagnesaemia, which ranged between 13.2% and 28.6%. Both non‐eligible studies investigating risk factors identified cisplatin as a risk factor. Carboplatin, nephrectomy and follow‐up time were other reported risk factors.
The prevalence of hypertension ranged from 0% to 50% in 2464 participants (30/52 studies). Risk factors reported by one eligible study were older age at screening and abdominal radiotherapy. A non‐eligible study also found long follow‐up time as risk factor. Three non‐eligible studies showed that a higher body mass index increased the risk of hypertension. Treatment‐related risk factors were abdominal radiotherapy and TBI, but studies were inconsistent.
Because of the profound heterogeneity of the studies, it was not possible to perform meta‐analyses. Risk of bias was present in all studies.
Authors' conclusions
The prevalence of adverse renal effects after treatment with cisplatin, carboplatin, ifosfamide, radiation therapy involving the kidney region, nephrectomy, or any combination of these, ranged from 0% to 84% depending on the study population, received treatment combination, reported outcome measure, follow‐up duration and methodological quality. With currently available evidence, it was not possible to draw solid conclusions regarding the prevalence of, and treatment‐related risk factors for, specific adverse renal effects. Future studies should focus on adequate study designs and reporting, including large prospective cohort studies with adequate control groups when possible. In addition, these studies should deploy multivariable risk factor analyses to correct for possible confounding. Next to research concerning known nephrotoxic therapies, exploring nephrotoxicity after new therapeutic agents is advised for future studies. Until more evidence becomes available, CCS should preferably be enrolled into long‐term follow‐up programmes to monitor their renal function and blood pressure.
Background
A decreased physical fitness has been reported in patients and survivors of childhood cancer. This is influenced by the negative effects of the disease and the treatment of childhood ...cancer. Exercise training for adult cancer patients has frequently been reported to improve physical fitness. In recent years, literature on this subject has also become available for children and young adults with cancer, both during and after treatment. This is an update of the original review that was performed in 2011.
Objectives
To evaluate the effect of a physical exercise training intervention on the physical fitness (i.e. aerobic capacity, muscle strength, or functional performance) of children with cancer within the first five years from their diagnosis (performed either during or after cancer treatment), compared to a control group of children with cancer who did not receive an exercise intervention.
To determine whether physical exercise within the first five years of diagnosis has an effect on fatigue, anxiety, depression, self efficacy, and HRQoL and to determine whether there are any adverse effects of the intervention.
Search methods
We searched the electronic databases of Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, and PEDro; ongoing trial registries and conference proceedings on 6 September 2011 and 11 November 2014. In addition, we performed a handsearch of reference lists.
Selection criteria
The review included randomized controlled trials (RCTs) and clinical controlled trials (CCTs) that compared the effects of physical exercise training with no training, in people who were within the first five years of their diagnosis of childhood cancer.
Data collection and analysis
Two review authors independently identified studies meeting the inclusion criteria, performed the data extraction, and assessed the risk of bias using standardized forms. Study quality was rated by the Grading of Recommendation Assessment, Development and Evaluation (GRADE) criteria.
Main results
Apart from the five studies in the original review, this update included one additional RCT. In total, the analysis included 171 participants, all during treatment for childhood acute lymphoblastic leukaemia (ALL).
The duration of the training sessions ranged from 15 to 60 minutes per session. Both the type of intervention and intervention period varied in all the included studies. However, the control group always received usual care.
All studies had methodological limitations, such as small numbers of participants, unclear randomization methods, and single‐blind study designs in case of one RCT and all results were of moderate to very low quality (GRADE).
Cardiorespiratory fitness was evaluated by the 9‐minute run‐walk test, timed up‐and‐down stairs test, the timed up‐and‐go time test, and the 20‐m shuttle run test. Data of the 9‐minute run‐walk test and the timed up‐and‐down stairs test could be pooled. The combined 9‐minute run‐walk test results showed significant differences between the intervention and the control groups, in favour of the intervention group (standardized mean difference (SMD) 0.69; 95% confidence interval (CI) 0.02 to 1.35). Pooled data from the timed up‐and‐down stairs test showed no significant differences in cardiorespiratory fitness (SMD ‐0.54; 95% CI ‐1.77 to 0.70). However, there was considerable heterogeneity (I2 = 84%) between the two studies on this outcome. The other two single‐study outcomes, 20‐m shuttle run test and the timed up‐and‐go test, also showed positive results for cardiorespiratory fitness in favour of the intervention group.
Only one study assessed the effect of exercise on bone mineral density (total body), showing a statistically significant positive intervention effect (SMD 1.07; 95% CI 0.48 to 1.66). The pooled data on body mass index showed no statistically significant end‐score difference between the intervention and control group (SMD 0.59; 95% CI ‐0.23 to 1.41).
Three studies assessed flexibility. Two studies assessed ankle dorsiflexion. One study assessed active ankle dorsiflexion, while the other assessed passive ankle dorsiflexion. There were no statistically significant differences between the intervention and control group with the active ankle dorsiflexion test; however, in favour of the intervention group, they were found for passive ankle dorsiflexion (SMD 0.69; 95% CI 0.12 to 1.25). The third study assessed body flexibility using the sit‐and‐reach distance test, but identified no statistically significant difference between the intervention and control group.
Three studies assessed muscle strength (knee, ankle, back and leg, and inspiratory muscle strength). Only the back and leg strength combination score showed statistically significant differences on the muscle strength end‐score between the intervention and control group (SMD 1.41; 95% CI 0.71 to 2.11).
Apart from one sub‐scale of the cancer scale (Worries; P value = 0.03), none of the health‐related quality of life scales showed a significant difference between both study groups on the end‐score. For the other outcomes of fatigue, level of daily activity, and adverse events (all assessed in one study), there were no statistically significant differences between the intervention and control group.
None of the included studies evaluated activity energy expenditure, time spent on exercise, anxiety and depression, or self efficacy as an outcome.
Authors' conclusions
The effects of physical exercise training interventions for childhood cancer participants are not yet convincing. Possible reasons are the small numbers of participants and insufficient study designs, but it can also be that this type of intervention is not as effective as in adult cancer patients. However, the first results show some positive effects on physical fitness in the intervention group compared to the control group. There were positive intervention effects for body composition, flexibility, cardiorespiratory fitness, muscle strength, and health‐related quality of life (cancer‐related items). These were measured by some assessment methods, but not all. However, the quality of the evidence was low and these positive effects were not found for the other assessed outcomes, such as fatigue, level of daily activity, and adverse events. There is a need for more studies with comparable aims and interventions, using a higher number of participants that also include diagnoses other than ALL.
Physical fitness and psychosocial function is often reduced in children during or shortly after cancer treatment. This study evaluates the effect of a combined physical exercise and psychosocial ...intervention on cardiorespiratory fitness, muscle strength, body composition, psychosocial function and health-related quality of life (HrQoL). In addition, intervention mediators, applicability and adherence were examined.
This multicenter randomized controlled trial included 68 children with cancer mean age 13.2 (SD: 3.1) years; 54% male during treatment or within 12-months post-treatment. The 12-week intervention consisted of 24 individual physical exercise sessions supervised by a physiotherapist, and 6 psychosocial training sessions for children and 2 for parents. Physical fitness and psychosocial function were assessed at baseline, directly post-intervention and at 12 months' post-baseline. Generalized estimating equations were used to simultaneously assess intervention effects at short and long-term. Additionally, we evaluated within-group differences over time. Potential physical and psychosocial mediators in the intervention effect on HrQoL were examined using the product-of-coefficient test. Applicability and adherence were assessed by trainer-report.
This study was able to compare 26 children who received the study intervention, with 33 children who received usual care. No significant differences in the effects of the intervention were found on physical fitness and psychosocial function at short-term. At 12-months follow-up, significantly larger improvements in lower body muscle strength (β = 56.5 Newton; 95% CI: 8.5; 104.5) were found in the intervention group when compared to the control group. Within-group changes showed significant improvements over time in HrQoL and bone density in both groups. Intervention effects on HrQoL were not significantly mediated by physical fitness and psychological function. Intervention applicability was satisfactory with an average session attendance of 67% and 22% dropout (mainly due to disease recurrence).
This 12-week physical exercise and psychosocial training intervention for children with cancer was applicable and showed satisfactory adherence. We found no significant between-group differences in effect, except for a significant improvement in lower body muscle strength at long-term in the intervention group compared to the control group. Yet, both the intervention and the control group showed improvements in bone mineral density and HrQoL over time.
The trial was registered at the Dutch Trial Registry ( NTR1531 ). Registered 12 November 2008.
The primary objective of this randomized study was to determine whether a continuous dosing schedule (without the asparaginase-free interval) would result in less hypersensitivity reactions to ...PEGasparaginase (PEGasp) compared with the standard noncontinuous dosing schedule.
Eight hundred eighteen patients (age 1-18 years) with ALL were enrolled in the Dutch Childhood Oncology Group-ALL11 protocol and received PEGasp. Three hundred twelve patients stratified in the medium-risk arm were randomly assigned to receive 14 individualized PEGasp doses once every two weeks in either a noncontinuous or continuous schedule after the first three doses in induction (EudraCT: 2012-000067-25). Hypersensitivity reactions were defined as allergies, allergic-like reactions, and silent inactivation. Secondary end points were other asparaginase-related toxicities, asparaginase activity and antibody levels, and outcome.
During induction, 27 of 818 patients (3.3%) experienced hypersensitivity reactions. After random assignment, 4 of 155 (2.6%) in the continuous treatment arm versus 17 of 157 (10.8%) patients in the noncontinuous treatment arm had hypersensitivity reactions (
< .01), of which two (1.3%) versus 13 (8.3%) were inactivating reactions (
< .01). The occurrence of inactivating hypersensitivity reactions was seven times lower in the continuous arm (odds ratio, 0.15 0.032-0.653). In addition, antibody levels were significantly lower in the continuous arm (
< .01). With exception of a lower incidence of increased amylase in the continuous arm, there were no significant differences in total number of asparaginase-associated toxicities between arms. However, the timing of the toxicities was associated with the timing of the asparaginase administrations. No difference in 5-year cumulative incidence of relapse, death, or disease-free survival was found between both treatment arms.
A continuous dosing schedule of PEGasp is an effective approach to prevent antibody formation and inactivating hypersensitivity reactions. The continuous PEGasp schedule did not increase toxicity and did not affect the efficacy of the therapy.
Abstract
BACKGROUND
Owing to a growing number of young and adolescent Hodgkin lymphoma (HL) survivors, awareness of (long-term) adverse effects of anticancer treatment increases. The risk of impaired ...reproductive ability is of great concern given its impact on quality of life. There is currently no review available on fertility after childhood HL treatment.
OBJECTIVE AND RATIONALE
The aim of this narrative review was to summarize existing literature on different aspects of reproductive function in male and female childhood, adolescent, and young adult HL survivors.
SEARCH METHODS
PubMed and EMBASE were searched for articles evaluating fertility in both male and female HL survivors aged <25 years at diagnosis. In females, anti-Müllerian hormone (AMH), antral follicle count, premature ovarian insufficiency (POI), acute ovarian failure, menstrual cycle, FSH, and pregnancy/live births were evaluated. In males, semen-analysis, serum FSH, inhibin B, LH, testosterone, and reports on pregnancy/live births were included. There was profound heterogeneity among studies and a lack of control groups; therefore, no meta-analyses could be performed. Results were presented descriptively and the quality of studies was not assessed individually.
OUTCOMES
After screening, 75 articles reporting on reproductive markers in childhood or adolescent HL survivors were included. Forty-one papers reported on 5057 female HL survivors. The incidence of POI was 6–34% (median 9%; seven studies). Signs of diminished ovarian reserve or impaired ovarian function were frequently seen (low AMH 55–59%; median 57%; two studies. elevated FSH 17–100%; median 53%; seven studies). Most survivors had regular menstrual cycles. Fifty-one studies assessed fertility in 1903 male HL survivors. Post-treatment azoospermia was highly prevalent (33–100%; median 75%; 29 studies). Long-term follow-up data were limited, but reports on recovery of semen up to 12 years post-treatment exist. FSH levels were often elevated with low inhibin B (elevated FSH 0–100%; median 51.5%; 26 studies. low inhibin B 19–50%; median 45%; three studies). LH and testosterone levels were less evidently affected (elevated LH 0–57%, median 17%; 21 studies and low testosterone 0–43%; median 6%; 15 studies). In both sexes, impaired reproductive ability was associated with a higher dose of cumulative chemotherapeutic agents and pelvic radiotherapy. The presence of abnormal markers before treatment indicated that the disease itself may also negatively affect reproductive function (Females: AMH<p10 9%; one study and Males: azoospermia 0–50%; median 10%; six studies). Reports on chance to achieve pregnancy during survivorship are reassuring, although studies had their limitations and the results are difficult to evaluate. In the end, a diminished ovarian reserve does not exclude the chance of a live birth, and males with aberrant markers may still be able to conceive.
WIDER IMPLICATIONS
This review substantiates the negative effect of HL treatment on gonadal function and therefore young HL survivors should be counseled regarding their future reproductive life, and fertility preservation should be considered. The current level of evidence is insufficient and additional trials on the effects of HL and (current) treatment regimens on reproductive function are needed. In this review, we make a recommendation on reproductive markers that could be assessed and the timing of (repeated) measurements.
Graphical Abstract
Graphical Abstract
Effects of treatment at <25 years of age on reproductive markers in survivors of Hodgkin lymphoma (HL).
Summary
Classical Hodgkin lymphoma (cHL) is characterised by malignant Hodgkin Reed–Sternberg cells located in an inflammatory microenvironment. Blood biomarkers result from active cross‐talk between ...malignant and non‐malignant cells. One promising biomarker in adult patients with cHL is thymus and activation‐regulated chemokine (TARC). We investigated TARC as marker for interim and end‐of‐treatment response in paediatric cHL. In this multicentre prospective study, TARC levels were measured among 99 paediatric patients with cHL before each cycle of chemotherapy and were linked with interim and end‐of‐treatment remission status. TARC levels were measured by enzyme‐linked immunosorbent assay. At diagnosis, TARC levels were elevated in 96% of patients. Plasma TARC levels declined significantly after one cycle of chemotherapy (p < 0.01 vs. baseline) but did not differ at interim assessment by positron emission tomography (p = 0.31). In contrast, median plasma TARC at end of treatment was significantly higher in three patients with progressive disease compared to those in complete remission (1.226 vs. 90 pg/ml; p < 0.001). We demonstrate that, in paediatric patients, plasma TARC is a valuable response marker at end‐of‐treatment, but not at interim analysis after the first two chemotherapy cycles. Further research is necessary to investigate TARC as marker for long‐term progression free survival.
Purpose
Cancer‐related fatigue is one of the most distressing side effects of childhood cancer treatment. Physical activity can decrease fatigue and has positive effects on other health outcomes. ...Most research on physical activity pertains to adults, and the few studies that focus on children have limited follow‐up time. This study evaluates cancer‐related fatigue in children and its association with physical activity over a one‐year time period.
Methods
Sixty‐eight children with cancer (7–18 years) were recruited during or within the first year after treatment. Physical activity (Actical activity monitor) and cancer‐related fatigue (Pediatric Quality‐of‐Life Questionnaire Multidimensional Fatigue Scale (PedsQL‐MFS), self‐ and parent‐ reports) were assessed at baseline, 4 months, and 12 months. PedsQL‐MFS scores were compared with Dutch norms. Longitudinal association of cancer‐related fatigue with physical activity was evaluated (No. NTR 1531).
Results
Generally, PedsQL‐MFS scores were worse than norms at baseline and 4 months, and recovered by 12 months except for the parent‐proxy scores in adolescents. Younger children (≤12 years) self‐reported comparable or better scores than norms. Physical activity generally improved over time, but patients mostly remained sedentary. During follow‐up, increased physical activity was associated with less cancer‐related fatigue.
Conclusion
Cancer‐related fatigue in children improves over time, and increased physical activity is associated with less cancer‐related fatigue. Given the sedentary lifestyle of this population, the positive effect of physical activity on cancer‐related fatigue, and the many other health benefits of an active lifestyle, it is important to stimulate physical activity in childhood cancer patients and survivors.
Although dexamethasone is highly effective in the treatment of pediatric acute lymphoblastic leukemia (ALL), it can cause serious metabolic side effects. Because studies regarding the effects of ...dexamethasone are limited by their small scale, we prospectively studied the direct effects of treating pediatric ALL with dexamethasone administration with respect to activation of components of metabolic syndrome (MetS); in addition, we investigated whether these side effects were correlated with the level of dexamethasone. Fifty pediatric patients (3-16 years of age) with ALL were studied during a 5-day dexamethasone course during the maintenance phase of the Dutch Childhood Oncology Group ALL-10 and ALL-11 protocols. Fasting insulin, glucose, total cholesterol, HDL, LDL, and triglycerides levels were measured at baseline (before the start of dexamethasone; T1) and on the fifth day of treatment (T2). Dexamethasone trough levels were measured at T2. We found that dexamethasone treatment significantly increased the following fasting serum levels (P<0.05): HDL, LDL, total cholesterol, triglycerides, glucose, and insulin. In addition, dexamethasone increased insulin resistance (HOMA-IR>3.4) from 8% to 85% (P<0.01). Dexamethasone treatment also significantly increased the diastolic and systolic blood pressure. Lastly, dexamethasone trough levels (N = 24) were directly correlated with high glucose levels at T2, but not with other parameters. These results indicate that dexamethasone treatment acutely induces three components of the MetS. Together with the weight gain typically associated with dexamethasone treatment, these factors may contribute to the higher prevalence of MetS and cardiovascular risk among survivors of childhood leukemia who received dexamethasone treatment.
Objective
The KLIK method is an online tool that monitors and discusses electronic patient‐reported outcomes (ePROs), which has been shown to enhance outcomes. This study aimed (1) to determine the ...fidelity (ie, extent to which used as intended) of the KLIK method as implemented in outpatient pediatric cancer care and (2) to study health care professional (HCP)‐reported barriers and facilitators for implementation.
Methods
Two hundred five children with newly diagnosed cancer (enrollment rate 85%) participated. At 1 (T1), 3 (T2), and 6 (T3) months after diagnosis, patients (8‐18 years) or parents (of patients 0‐7 years) completed health‐related quality of life (HRQoL) questionnaires, which were transformed into an ePROfile and discussed by their HCP during consultations. Fidelity was determined by the following: percentage of website registrations, HRQoL questionnaires completed, and ePROfiles discussed. Implementation determinants were assessed with HCPs after the final T3 with the Measurement Instrument for Determinants of Innovations.
Results
Depending on the time point (T1‐T3), fidelity was 86% to 89% for website registration, 66‐85% for completed HRQoL questionnaires, and 56% to 62% for ePROfile discussion. Barriers were mainly related to organizational issues (eg, organizational change) and less frequently to users (eg, motivation to comply) or the intervention (compatibility). Facilitators were related to the user (eg, positive outcome expectations) and intervention (simplicity) but not to the organization.
Conclusions
When implementing ePROs in outpatient pediatric oncology practice, HCPs report determinants that influence ePRO integration. To improve implementation and outcomes, tailored organizational (eg, formal ratification by management and time) and specific local (eg, individualized assessments) strategies should be developed to achieve optimal ePRO discussion.
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